RESUMO
AIMS: Patients with schizophrenia frequently show insufficient vitamin D levels, which are associated with somatic comorbidity and may contribute to psychopathology. For many reasons, vitamin D supplementation may be indicated for this patient cohort. However, there is growing evidence for a vitamin D-mediated increase of drug metabolism by induction of cytochrome P450 (CYP) 3A4. Hence, this study aimed to assess vitamin D's impact on both antipsychotic drug concentrations and psychopathology in a non-interventional manner. METHODS: Totals of 107 serum concentrations of different antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine and risperidone), 80 serum concentrations of vitamin D and psychopathological assessments were obtained from 80 patients with schizophrenia. The impact of Vitamin D on antipsychotic drug concentrations and symptomatology was assessed using a generalized linear model, path and correlation analyses. RESULTS: We observed a negative relationship between vitamin D and dose-adjusted antipsychotic drug concentrations, which was particularly pronounced for drugs which are predominantly metabolized via CYP3A4 (i.e., aripiprazole and quetiapine). A path analysis suggested a relieving effect of vitamin D on symptomatology which was, however, counteracted by its negative impact on antipsychotic drug levels. Finally, patients with vitamin D levels above the median exhibited a significantly higher proportion of therapeutically insufficient dose-normalized drug concentrations of aripiprazole and quetiapine. CONCLUSION: Despite vitamin D's potential benefits on physical and mental health, clinicians should be aware of its negative impact on blood concentrations of antipsychotics metabolized by CYP3A4 in patients with schizophrenia. Therefore, when considering its supplementation, therapeutic drug monitoring should be applied to guide dose adjustment.
Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Benzodiazepinas/efeitos adversos , Citocromo P-450 CYP3A , Humanos , Fumarato de Quetiapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Vitamina DRESUMO
BACKGROUND: Autoenucleation is a rare form of self-mutilation typically associated with psychiatric disorders such as schizophrenia, substance-induced psychosis and bipolar disorder. The act is usually unilateral, although bilateral attempts are also well documented in the literature. CASE PRESENTATION: It is a case study involving a female patient (NN) diagnosed with schizoaffective disorder who self-enucleated her right eye following sexual intercourse with a fellow patient, and was forcefully prevented by staff from enucleating the second eye. We report recurrent episodes of her illness culminating in this severe act of self-mutilation. The motivational reasons behind this form of self-harm along with differential diagnosis and potential treatment options are discussed in the context of the available literature. CONCLUSION: Autoenucleation is commonly associated with religious and sexual delusions, and patients are thought to be at a greater risk of further self-harm. Timely antipsychotic treatment is likely to reduce the risk of such extreme forms of self-harm, although they can occur despite robust therapeutic intervention and treatment attempts. While self-inflicted eye injuries are rare, their prevention in what is typically a difficult patient group is fraught with challenges.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Automutilação , Comportamento Autodestrutivo , Adulto , Feminino , Humanos , Transtornos Psicóticos/diagnósticoRESUMO
Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies.
Assuntos
Encefalomielite Autoimune Experimental/patologia , Esclerose Múltipla/patologia , Animais , Axônios/patologia , Axônios/ultraestrutura , Encefalomielite Autoimune Experimental/imunologia , Feminino , Cinética , Vértebras Lombares , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Proteína Proteolipídica de Mielina/imunologia , Bainha de Mielina/patologia , Bainha de Mielina/ultraestrutura , Glicoproteína Mielina-Oligodendrócito/imunologia , Fragmentos de Peptídeos/imunologia , Proteínas Recombinantes de Fusão/imunologia , Medula Espinal/patologia , Medula Espinal/ultraestruturaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0144847.].
RESUMO
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP) fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE) in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS. METHODS: Twenty-two female C57BL/6 (B6) mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE) was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE) and six months after onset of EAE (long-term EAE). The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT) of the spinal cord. RESULTS: B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND) as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG) model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation. CONCLUSIONS: Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse histopathological aspects of MS.